Abstract Obese patients represent the majority of patients with poorly controlled asthma in the United States. Obese asthmatics do not respond as well to standard controller therapies (such as inhaled corticosteroids and long acting beta agonists) as lean asthmatics, and have increased asthma exacerbations compared with lean asthmatics. There is an urgent need to develop new therapies to treat obese patients with asthma. One potential therapy for the treatment of obese asthmatics is the phospohodiesterase 4 inhibitor roflumilast. This medication, currently approved for the treatment of patients with chronic obstructive pulmonary disease, has a number of effects that make it particularly exciting as a potential therapy for obese asthmatics: roflumilast has direct effects on inflammation and remodeling in the airway, and there is preliminary data supporting efficacy in asthma; roflumilast has beneficial metabolic effects that may be useful in the treatment of asthma in obesity; finally, roflumilast induces weight loss, which may also lead to improved asthma control in obese patients. The current proposal comprises two pilot studies to be performed with the American Lung Association?s Airways Clinical Research Centers network: a pilot randomized, placebo-controlled trial of Roflumilast in obese patients with poorly controlled asthma at six centers, and a feasibility study across the entire network. These pilot protocols will be used to determine feasibility and inform the development of a definitive multicenter clinical trial of roflumilast in obese patients with poorly controlled asthma. If ultimately successful roflumilast would represent the first treatment specifically targeted towards obese patients with asthma, a patient population that is refractory to current therapies, and represents the majority of poorly controlled asthmatics in the United States.